The Peoples Republic of China has the second highest incidence of TB in the world, with a 2004 estimated rate of 101 cases/100,000 persons/year. Based on data collected in the 4th national TB epidemiological survey in 2000, it is estimated that there were 1.96 million pulmonary TB cases. With an estimated MDR-TB prevalence of 10.7%, there were 209,720 cases of pulmonary, bacteriologically confirmed MDR-TB in China in 2000. Of note, about half of all prevalent cases of TB disease in 2000 were extrapulmonary. Much of this MDR disease is concentrated in specific regions of China with Henan Province in central China having the highest total number of reported cases. In partnership with provincial health authorities in Zheng Zhou, the Capitol city of Henan Province, the Tuberculosis Research Section intends to develop the capacity to conduct high-quality clinical research. Therefore, in 2009 NIAID Deputy Director Hugh Auchincloss signed a letter of intent with the Henan Provincial Bureau of Health to establish a collaborative research center. In response the provincial government has begun construction of a new infectious disease hospital to house the research facility and better accommodate the heavy burden of patients in Henan Province. A prospective, longitudinal Natural History study entitled "A Natural History Study of Tuberculosis in China: Correlates of a Successful Response in Treatment" (NIAID 10-I-N060) was approved by the NIAID IRB and enrollment commenced after lab renovation and installation of equipment in July 2010. This protocol will enroll and monitor 150 subjects with suspected TB at the Henan Provincial Chest Hospital. The subjects are divided into three cohorts according to their diagnosis: A) Acid-fast bacilli (AFB) smear positive pulmonary tuberculosis, B) AFB smear negative pulmonary tuberculosis, and C) extra pulmonary tuberculosis (EPTB) and these subjects will be followed during their initial response to antituberculous chemotherapy. 25 healthy controls (Cohort D) will also be enrolled to determine baseline values for immunologic responses and laboratory values. This study will be looking at the change in total volume of disease as assessed by quantitative CT scanning at baseline, 2 and 6 months. In addition, we will monitor chemotherapeutic regimens, changes in the host immune response, overall changes in clinical parameters, initial and acquired drug-resistance of the infecting isolates, and changes in bacterial and host markers in subject samples during chemotherapy. In each case, we will look for associations of these parameters with rates of disease resolution correlated with specific structural features determined by CT scanning the site of TB disease. This study will allow us to evaluate eligibility criteria for future clinical trials, establish TB diagnostic accuracy, understand standard of care initial regimen selection and subsequent modifications, evaluate mycobacterial strain characteristics, extent of disease, types of lesions and host immunologic response to chemotherapy, as well as identify surrogate markers for improving monitoring of the response to chemotherapy. As of August 1 2011, 133 subjects have been enrolled into the study;Cohort A is fully enrolled, there are 37 subjects in both Cohort B and Cohort C, and 9 subjects are enrolled in Cohort D. Sixty-four subjects have completed the study to date. Study personnel are culturing bacteria from sputa and other samples, collecting and freezing plasma, performing gamma interferon stimulation assays, and filling out case report forms on a regular basis. The Open Clinica database designed for the study that was released last year is being used by the data entry personal allowing monitoring the progress of the study remotely. The study team is performing QuantiFERON (QFT) testing and two molecular tests for establishing drug resistance. The QFT test uses whole blood to detect interferon gamma production in response to mycobacterial antigens iin serial samples collected prior to and during anti-tubercular treatment. The QFT ELISA tests were completed for all samples of 25 subjects who had completed the study and analysis is underway. In addition, bacterial DNA was isolated from cultured sputa and/or sputum sediment and was used to detect Rifampicin and Isoniazid resistance (Hain test) and speciate non-tuberculous mycobacteria (NTM) (Reverse line blot assay). Among the subject specimens tested thus far 10% were determined to be multidrug resistant by the Hain test and 5% contained predominantly NTM based on the Reba results. Two of the 3 NTMs were identified as M. intracellulare and both were subjects that had had a history of TB treatment. While the rate of MDR-TB appears lower than might be expected in a tertiary hospital, 80% of subjects enrolled in the study have never been previously treated for TB. Half of the confirmed MDR-TB cases have occurred in subjects that were treatment naive suggesting on-going primary transmission of MDR-TB in this study population.